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Chromosome 9p-linked families with frontotemporal dementia associated with motor neuron disease.

Abstract：

BACKGROUND:Frontotemporal dementia associated with motor neuron disease (FTD-MND) is a rare neurodegenerative disorder that may be inherited by autosomal dominant trait. No major gene has been identified but a locus was mapped on chromosome 9 (9p21.3-p13.3). METHODS:Ten French families with FTD-MND were tested for linkage to the 9p21.3-p13.3 region. We report extensive mutation screening in 9p-linked families and their clinical characteristics. RESULTS:We identified six new families with evidence for linkage to the chromosome 9p. Cumulative multipoint LOD score values were positive between markers D9S1121 and D9S301, reaching a peak of 8.0 at marker D9S248. Haplotype reconstruction defined the telomeric boundary at marker AFM218xg11, slightly narrowing the candidate interval. We found no disease-causing mutations by sequencing 29 candidate genes including IFT74 and no copy number variations in the 9p region. The mean age at onset was 57.9 +/- 10.3 years (range, 41-84), with wide heterogeneity within and among families suggesting age-dependant penetrance. The patients presented isolated FTD (32%), isolated MND (29%), or both disorders (39%). The general characteristics of the disease did not differ, except for an older age at onset and shorter disease duration in the 9p-linked compared to nonlinked families. TDP-43-positive neuronal cytoplasmic inclusions were found in cortex and spinal cord in 3 patients. CONCLUSIONS:This study increases the number of 9p-linked families now reported and shows that this locus may have a major effect on frontotemporal dementia (FTD) and motor neuron disease (MND). Considering our results, the causative gene might be implicated in at least 60% of the families with FTD-MND disorder.

journal_name

Neurology

journal_title

Neurology

authors

Le Ber I,Camuzat A,Berger E,Hannequin D,Laquerrière A,Golfier V,Seilhean D,Viennet G,Couratier P,Verpillat P,Heath S,Camu W,Martinaud O,Lacomblez L,Vercelletto M,Salachas F,Sellal F,Didic M,Thomas-Anterion C,Puel M

doi

10.1212/WNL.0b013e3181a55f1c

subject

Has Abstract

pub_date

2009-05-12 00:00:00

pages

1669-76

issue

eissn

0028-3878

issn

1526-632X

pii

72/19/1669

journal_volume

pub_type

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Chromosome 9p-linked families with frontotemporal dementia associated with motor neuron disease.